Blaydon, D.C., Nitoiu, D., Eckl, K.M., Cabral, R.M., Bland, P., Hausser, I., van Heel, D.A., Rajpopat, S., Fischer, J., Oji, V., Zvulunov, A., Traupe, H., Hennies, Hans C. and Kelsell, D.P. (2011) Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. The American Journal of Human Genetics, 89 (4). pp. 564-571. ISSN 0002-9297Metadata only available from this repository.
Autosomal-recessive exfoliative ichthyosis presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of nonerythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Using whole-genome homozygosity mapping, candidate-gene analysis and deep sequencing, we have identified loss-of-function mutations in the gene for protease inhibitor cystatin A (CSTA) as the underlying genetic cause of exfoliative ichthyosis. We found two homozygous mutations, a splice-site and a nonsense mutation, in two consanguineous families of Bedouin and Turkish origin. Electron microscopy of skin biopsies from affected individuals revealed that the level of detachment occurs in the basal and lower suprabasal layers. In addition, in vitro modeling suggests that in the absence of cystatin A protein, there is a cell-cell adhesion defect in human keratinocytes that is particularly prominent when cells are subject to mechanical stress. We show here evidence of a key role for a protease inhibitor in epidermal adhesion within the lower layers of the human epidermis.
|Additional Information:||Unmapped bibliographic data: ST - Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion [Field not mapped to EPrints] C2 - PMC3188842 [Field not mapped to EPrints] AD - Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK. [Field not mapped to EPrints] AN - 21944047 [Field not mapped to EPrints]|
|Uncontrolled Keywords:||Amino Acid Sequence|
|Subjects:||Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
|Schools:||School of Applied Sciences|
|Depositing User:||Hans Hennies|
|Date Deposited:||11 Jul 2016 14:19|
|Last Modified:||29 Jul 2016 13:13|
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